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Biomedical subjects

Javier Salvador

Publications and source records attributed to Javier Salvador.

10 recordsLinked to original sources
PubMed2004

Fasting plasma ghrelin concentrations 6 months after gastric bypass are not determined by weight loss or changes in insulinemia.

BACKGROUND: Ghrelin is a gastric peptide with potent orexigenic effects. Circulating ghrelin concentrations are increased in obese subjects, but increase after weight loss. However, in patients undergoing Roux-en-Y gastric bypass (RYGBP), a decrease in ghrelin levels has been reported. The effect of comparable weight loss induced by either adjustable gastric banding (AGB), RYGBP or conventional dietary treatment (Conv) on ghrelinemia was studied. METHODS: 24 matched obese male patients in whom similar weight loss had been achieved by either AGB (n=8), RYGBP (n=8) or Conv (n=8) were studied before and 6 months after treatment start. The independence of ghrelin concentrations from body mass index (BMI) and weight loss was further analyzed in a group of patients with total gastrectomy (TtGx, n=6). RESULTS: Comparable weight loss after 6 months exerted significantly different effects on plasma ghrelin concentrations, depending on the procedure applied (AGB: 424.6 +/- 32.8 pg/ml; RYGBP: 131.4 +/- 13.5; Conv: 457.3 +/- 18.7; P<0.001). Without significant differences in body weight and BMI, patients who had undergone the RYGBP exhibited a statistically significant decrease in fasting ghrelin concentrations, while the other two procedures (AGB and Conv) showed a weight loss-induced increase in ghrelin levels. Despite significant differences in BMI between RYGBP and TtGx patients after 6 months (31.9 +/- 2.2 vs 22.0 +/- 0.7 kg/m(2), respectively; P<0.05), both groups showed similar ghrelin concentrations. CONCLUSION: The reduction in circulating ghrelin concentrations in RYGBP patients after 6 months of surgery are not determined by an active weight loss or an improved insulin-sensitivity but rather depend on the surgically-induced bypass of the ghrelin-producing cell population of the fundus.

Adult↗
PubMed2004

The decrease in plasma ghrelin concentrations following bariatric surgery depends on the functional integrity of the fundus.

BACKGROUND: Gastric bypass surgery, which involves the production of a reduced stomach pouch,has been shown to markedly suppress circulating ghrelin concentrations. Since bypassing the ghrelin-producing cell population may be relevant to the disruption of fundic-derived factors participating in food intake signaling, the effect of weight loss induced by either adjustable gastric banding (AGB), Roux-en-Y gastric bypass (RYGBP) or biliopancreatic diversion (BPD) was studied. METHODS: 16 matched obese patients [35.0 + 2.4 years; initial body weight 124.8 +/- 5.7 kg; body mass index (BMI) 47.1 +/- 2.2 kg/m(2)] in whom similar weight loss had been achieved by either AGB (n=7), RYGBP (n=6) or BPD (n=3) were studied. Blood was obtained for biochemical and hormonal analyses. Body composition was assessed by air-displacement-plethysmography. RESULTS: Comparable weight loss (AGB: 26.1 +/- 5.1 kg; RYGBP: 32.1 +/- 5.0; BPD: 31.7 +/- 6.1; P=NS) and decrease in percentage body fat (AGB: 10.0 +/- 1.5%; RYGBP: 14.2 +/- 2.8; BPD: 10.3 +/- 1.0; P=NS) induced by bariatric surgery exerted significantly different (P=0.004) effects on plasma ghrelin concentrations, depending on the surgical procedure applied (AGB: 480 +/- 78 pg/ml; RYGBP: 117 +/- 34; BPD: 406 +/- 86). Without significant differences in BMI, body fat, glucose, triglycerides, cholesterol, insulin and leptin levels, patients who had undergone the RYGBP exhibited statistically significant diminished circulating fasting plasma ghrelin concentrations compared with the other two bariatric techniques which conserve direct contact of the fundus with ingested food (P=0.003 vs AGB and P=0.020 vs BPD). CONCLUSION: Fasting circulating ghrelin concentrations in patients undergoing diverse bariatric operations depend on the degree of dysfunctionality of the fundus.

Adult↗
PubMed2003

Gene expression profile of omental adipose tissue in human obesity.

The aim of the present study was to gain insight into the pathophysiology of obesity by comparing the pattern of gene expression of omental adipose tissue of obese and lean volunteers using DNA microarrays. Omental adipose tissue biopsies were obtained by laparoscopic surgery from six male patients (44.2+/-6.3 yr). RNA was extracted and pooled for the obese (BMI: 37.3+/-2.5 kg/m2) and lean (BMI: 23.4+/-0.8 kg/m2) groups. From the total number of genes analyzed (1,152 well-characterized human genes), 41% were expressed at sufficient levels in human adipose tissue for detection in the microarray experiments, finding that 89 genes were up-regulated while 64 were down-regulated at least twofold in the omental adipose tissue obtained from obese patients. We found a general tendency to blunt lipolysis inducer genes and a global down-regulation of genes encoding growth factors. Moreover, an up-regulation in the expression of several mitogen-activated protein kinases (MAPKs) was observed. The down-regulation of genes involved in lipolysis activation may be involved in the etiopathogenesis of obesity. In addition, down-regulation of growth factors and the up-regulation of MAPKs may indicate an attempt to restrain adipocyte proliferation and differentiation. Furthermore, obesity is accompanied by an altered expression in omental adipose tissue of genes involved not only in energy homeostasis but also in quite diverse biological functions, such as immune response. The genomic approach underlines the importance of adipose tissue beyond energy metabolism.

Adipose Tissue↗
PubMed2003

A multicenter phase II study of irinotecan (CPT-11) alternated with 5-fluorouracil and leucovorin as first-line treatment of patients with metastatic colorectal cancer.

PURPOSE: In this multicenter phase II study the efficacy and safety of the alternating schedule of irinotecan (CPT-11) with bolus 5-fluorouracil (5-FU) and leucovorin (LV) were assessed as first-line chemotherapy in patients with metastatic colorectal cancer (CRC). PATIENTS AND METHODS: Enrolled in the study were 43 patients with advanced CRC. They received CPT-11 350 mg/m2 i.v. on day 1, alternating with LV 20 mg/m2 i.v. and 5-FU 425 mg/m2 i.v. daily for five consecutive days, on days 22-26 (Mayo Clinic regimen). One cycle consisted of 6 weeks. RESULTS: A total of 179 cycles were administered with a median of four per patient (range one to nine). Efficacy was analyzed on an intention-to-treat basis. The overall objective response rate was 30% (95% CI 16-44), with four complete responses and nine partial responses, whereas 20 patients (4%) showed stable disease. The median time to disease progression was 9.0 months and median survival was 18.5 months. Grade 3/4 diarrhea was mainly related to CPT-11 rather than to 5-FU (9.3% vs 4.7% of patients), whereas grade 3/4 neutropenia was higher during 5-FU administration (16.3% vs 7.0% of patients). CONCLUSIONS: The alternating schedule of CPT-11 with 5 days bolus of 5-FU and low-dose LV showed a clinical benefit in terms of tumor growth control as first-line treatment of patients with metastatic CRC. The overall safety data confirmed this alternating combination as a well-tolerated treatment.

Adolescent↗
PubMed2002

Involvement of leptin in the association between percentage of body fat and cardiovascular risk factors.

OBJECTIVES: Recent epidemiologic studies have shown that obesity is associated with elevated blood concentrations of prothrombotic-proinflammatory factors and markers of endothelial dysfunction such as fibrinogen, C-reactive protein (CRP), von Willebrand factor (vWF), and homocysteine. We have assessed whether these markers are associated with percentage of body fat (BF), insulin sensitivity as well as with leptin concentrations. DESIGN AND METHODS: Twenty-five men aged 49.6 +/- 12.7 yr (mean +/- SD) underwent whole-body air displacement plethysmography (Bod-Pod(R)) for estimating BF. Blood analyses for leptin and several other metabolic and cardiovascular markers were carried out. RESULTS: Obese subjects had higher levels as compared to controls of BF (37.5 +/- 5.1 vs. 26.0 +/- 6.6, p < 0.01), fibrinogen (3.30 +/- 0.43 vs. 2.67 +/- 0.11, p < 0.01), vWF (136.4 +/- 50.4% vs. 81.6 +/- 12.6%, p < 0.05), and leptin (17.6 +/- 8.7 vs. 6.2 +/- 3.3, p < 0.01), lower concentrations of HDL-cholesterol (1.09 +/- 0.20 vs. 1.51 +/- 0.10, p < 0.001) and lower QUICKI (1/[log(Ins(0)) + log(Glu(0))]) (0.31 +/- 0.03 vs. 0.34 +/- 0.02, p < 0.05). No significant changes were observed in CRP (5.7 +/- 3.4 vs. 3.8 +/- 1.6, p = 0.327) and homocysteine (9.4 +/- 4.2 vs. 8.3 +/- 0.9, p = 0.749). A positive correlation was observed between BF and fibrinogen (r = 0.67, p = 0.0003). Plasma leptin concentrations were correlated with fibrinogen (r = 0.71, p = 0.0001) and CRP (r = 0.43, p = 0.044). After adjustment for BF leptin emerged as a significant predictor of fibrinogen (beta = 0.47, p = 0.023; R(2) = 0.59, p < 0.001). QUICKI was positively correlated with HDL-cholesterol (r = 0.59, p = 0.010) and negatively with fibrinogen (r = -0.53, p = 0.025), CRP (r = -0.52, p = 0.028) and vWF (r = -0.56, p = 0.013). CONCLUSIONS: Increased BF and impaired insulin sensitivity are associated with increased concentrations of cardiovascular risk factors. Leptin seems to be involved in this elevation and emerges as a predictor of circulating fibrinogen concentrations.

Adipose Tissue↗
PubMed2002

Leptin inhibits angiotensin II-induced intracellular calcium increase and vasoconstriction in the rat aorta.

Besides its role in body weight control leptin may also act as a vasoactive hormone. This study was designed to investigate whether leptin modifies angiotensin II (ANG II)-induced vascular responses. The expression of functional leptin receptors (OB-Rb) was detected in vascular smooth muscle cells (VSMCs) from adult Wistar rats by RT-PCR. Immunocytochemistry and Western blot analysis further showed the expression of OB-R protein in VSMCs. The ANG II (10(-7) mol/liter)-induced increase in intracellular Ca(2+) was blocked (P < 0.01) by leptin (10(-8) mol/liter). Moreover, in calcium-free buffer leptin was able to inhibit 65% of the ANG II-induced calcium release from intracellular stores. In endothelium-denuded aortic rings from adult Wistar rats no effect of leptin on basal tension was observed. However, the ANG II-induced isometric contraction was reduced (P < 0.05) by leptin (10(-8) mol/liter). The experiments were also performed in age- and sex-matched Zucker rats, in which no effect of leptin on ANG II-induced calcium increase and vasoconstriction was observed. It is concluded that leptin blocks the vasoconstrictor action of ANG II and inhibits the ANG II-induced increase in intracellular Ca(2+) in VSMCs through OB-Rb. These findings provide new insight into the physiological effects of leptin on blood pressure regulation.

Angiotensin II↗
PubMed2002

Disruption of the leptin-insulin relationship in obese men 24 hours after laparoscopic adjustable silicone gastric banding.

BACKGROUND: The placement of a band to attain a tiny stomach pouch has been reported to produce early satiety in patients undergoing gastric banding. The adipocyte-derived hormone, leptin, has been shown to decrease both food intake and body weight. The aim of the present study was to assess the potential involvement of acute changes in leptin concentrations following laparoscopic adjustable silicone gastric banding (LASGB). METHODS: The study groups comprised obese male patients undergoing bariatric surgery by LASGB and overweight men undergoing laparoscopic Nissen fundoplication (NFd). Blood was drawn before surgery and 24 hours postoperatively for glucose, insulin and leptin measurements. RESULTS: In both experimental groups, a statistically significant decrease was observed in pre- and postsurgery glucose (LASGB 111 +/- 8 vs 99 +/- 6 mg/dl, P < 0.01; NFd 107 +/- 7 vs 98 +/- 5 mg/d, P < 0.01) and insulin concentrations (LASGB 39.8 +/- 11.9 vs 32.9 +/- 10.3 U/l, P < 0.01; NFd 13.2 +/- 3.3 vs 12.2 +/- 2.9 U/l, P < 0.05). However, no significant differences were observed when the percent change from pre-surgery values was analysed between both groups. Following surgery, an increase in leptin concentrations was observed in the LASGB group (23.5 +/- 4.7 vs 37.5 +/- 6.8 micrograms/l, P < 0.001) whereas a small decrease was evident in the NFd patients (12.9 +/- 4.6 vs 8.9 +/- 2.2 micrograms/l, P < 0.01). CONCLUSION: These findings strongly suggest that the short-term increase observed in plasma leptin concentrations following LASGB may play a key role in triggering an early satiety signal due to the modification of the gastrointestinal anatomy and physiology.

Adult↗